B Vitamins Don't Cut Colorectal Adenoma Risk

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This was a randomized study designed to assess the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma.

Note that the data indicate no statistically significant effect of combined B-vitamin treatment on the incidence of colorectal adenoma among women at high risk for cardiovascular disease.

Among women at high risk for cardiovascular disease, daily supplementation with a combination of folic acid, vitamin B6, and vitamin B12 did not affect the risk of colorectal adenoma, a post hoc analysis of a randomized trial showed.

The rate of incident colorectal adenomas was similar in women who received supplementation and those who received placebo for up to 7.3 years (24.3% versus 24%; RR 1.00, 95% CI 0.83 to 1.20), according to Shumin Zhang, MD, ScD, of Brigham and Women's Hospital in Boston, and colleagues.

There were no subgroups in which supplementation was associated with benefit or harm, the researchers reported online in the Journal of the National Cancer Institute.

"Our findings do not support recommending B-vitamin supplementation for the prevention of colorectal adenomas," they wrote. "Further evidence, ideally from large, well-designed randomized controlled trials with long-term follow-up or from large longitudinal studies, is needed to confirm our findings."

Folic acid, vitamin B6, and vitamin B12 are all involved in one-carbon metabolism, which is necessary for DNA synthesis, repair, and methylation. Laboratory animal studies have suggested that the B vitamins may protect against colorectal carcinogenesis.

Observational studies in humans have supported that idea, with several showing associations between higher levels of folate or vitamin B6 in the blood and a lower risk of colorectal neoplasia. Randomized trials mostly involving folic acid supplementation alone, however, have not revealed an effect on colorectal adenomas.

Zhang and colleagues explored a possible link between supplementation with B vitamins and the development of colorectal adenomas using data from the Women's Antioxidant and Folic Acid Cardiovascular Study, which evaluated the daily use of the combination of folic acid, vitamin B6, and vitamin B12 for the prevention of cardiovascular disease in female health professionals at high cardiovascular risk. Participants were at least 40 years old and postmenopausal.

A previous analysis of trial data by the researchers showed that the supplement had no effect on overall invasive cancer risk or risk of colorectal cancer.

The current analysis looking at colorectal adenomas included 1,470 women (mean age 62) who were followed during up to 7.3 years of treatment and up to 1.9 years post-treatment, and who underwent at least one endoscopy during the study.

The lack of a between-group difference in the risk of colorectal carcinoma was consistent across subgroups defined by adenoma subsite, size, and stage, number of adenomas, and patient characteristics.

Alcohol intake, history of cancer or adenoma, and baseline plasma levels or intake of folate, vitamin B6, and vitamin B12 did not significantly affect the relationship.

In an accompanying editorial, Regina Ziegler, PhD, MPH, of the National Cancer Institute's Division of Cancer Epidemiology and Genetics in Bethesda, Md., said that the findings of the study are consistent with a meta-analysis of three large, randomized, placebo-controlled trials of folic acid supplementation conducted in the U.S., Canada, the U.K., and Denmark.

But, she said, "although these randomized trials do suggest that high-dose folic acid is not a promising chemopreventive agent for colorectal cancer, they do not completely resolve the role of folate and other B vitamins in colorectal carcinogenesis."

She pointed to the observational studies that have supported an association between increased folate intake -- both through the diet and through supplements -- and a lower risk of colon cancer.

"These observational epidemiology results ... are provocative and imply that the role of folate and other B vitamins in colorectal carcinogenesis merits continued exploration," Ziegler wrote.

Zhang and colleagues acknowledged some limitations of their analysis, including the inability to examine the individual components of the combination pill separately, possible confounding by additional factors, and uncertain generalizability to men and women with lower cardiovascular risk.

The study was funded by the American Cancer Society and the National Institutes of Health. Vitamin E and its placebo were supplied by Cognis Corporation. All other agents and their placebos were supplied by BASF Corporation. Pill packaging was provided by Cognis and BASF.

The study authors did not make any additional financial disclosures.

Ziegler reported funding from the Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. She said she had no conflicts of interest.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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